Trial Outcomes & Findings for A Study in Participants With Type 1 Diabetes Mellitus (NCT NCT01481779)
NCT ID: NCT01481779
Last Updated: 2018-04-17
Results Overview
HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM), adjusting for treatment, stratification factors (baseline low-density lipoprotein cholesterol \[LDL-C\] \[\<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
COMPLETED
PHASE3
455 participants
26 weeks
2018-04-17
Participant Flow
Participant milestones
| Measure |
LY2605541 + Insulin Lispro
LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
295
|
160
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
294
|
159
|
|
Overall Study
COMPLETED
|
225
|
132
|
|
Overall Study
NOT COMPLETED
|
70
|
28
|
Reasons for withdrawal
| Measure |
LY2605541 + Insulin Lispro
LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
23
|
5
|
|
Overall Study
Lost to Follow-up
|
3
|
2
|
|
Overall Study
Protocol Violation
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
26
|
13
|
|
Overall Study
Physician Decision
|
13
|
4
|
|
Overall Study
Sponsor Decision
|
3
|
1
|
Baseline Characteristics
A Study in Participants With Type 1 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
LY2605541 + Insulin Lispro
n=295 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=160 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Total
n=455 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.68 years
STANDARD_DEVIATION 12.93 • n=5 Participants
|
38.91 years
STANDARD_DEVIATION 14.10 • n=7 Participants
|
39.41 years
STANDARD_DEVIATION 13.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
157 Participants
n=5 Participants
|
73 Participants
n=7 Participants
|
230 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
138 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
225 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
33 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
153 Participants
n=5 Participants
|
85 Participants
n=7 Participants
|
238 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
109 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
168 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
63 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
221 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
346 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
23 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
85 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
25 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
27 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
45 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
60 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM), adjusting for treatment, stratification factors (baseline low-density lipoprotein cholesterol \[LDL-C\] \[\<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Hemoglobin A1c (HbA1c) at 26 Weeks
|
7.06 percentage of HbA1c
Standard Error 0.04
|
7.43 percentage of HbA1c
Standard Error 0.06
|
SECONDARY outcome
Timeframe: 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Hemoglobin A1c (HbA1c)
Week 52
|
7.30 percentage of HbA1c
Standard Error 0.05
|
7.55 percentage of HbA1c
Standard Error 0.06
|
|
Hemoglobin A1c (HbA1c)
Week 78
|
7.43 percentage of HbA1c
Standard Error 0.05
|
7.70 percentage of HbA1c
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 52 weeks, 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Week 26
|
-0.69 percentage of HbA1c
Standard Error 0.04
|
-0.33 percentage of HbA1c
Standard Error 0.06
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Week 56
|
-0.46 percentage of HbA1c
Standard Error 0.05
|
-0.21 percentage of HbA1c
Standard Error 0.06
|
|
Change From Baseline in Hemoglobin A1c (HbA1c)
Week 78
|
-0.33 percentage of HbA1c
Standard Error 0.05
|
-0.05 percentage of HbA1c
Standard Error 0.07
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.
HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, then multiplying by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c ≤6.5%, Week 26
|
28.6 percentage of participants
|
13.7 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c ≤6.5%, Week 52
|
23.3 percentage of participants
|
13.1 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c ≤6.5%, Week 78
|
20.2 percentage of participants
|
13.1 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c <7.0%, Week 26
|
44.9 percentage of participants
|
27.5 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c <7.0%, Week 52
|
37.3 percentage of participants
|
28.1 percentage of participants
|
|
Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
HbA1c <7.0%, Week 78
|
34.5 percentage of participants
|
22.9 percentage of participants
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data. Missing endpoints were imputed with the LOCF method.
Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c \<7.0% without nocturnal hypoglycemia by the total number of participants analyzed, then multiplying by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia
Week 26
|
3.8 percentage of participants
|
2.0 percentage of participants
|
|
Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia
Week 52
|
2.1 percentage of participants
|
0.7 percentage of participants
|
|
Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia
Week 78
|
1.0 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log \[exposure in days/30\] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=293 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Total Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 26
|
16.01 episodes/participant/30 days
Standard Error 0.44
|
12.43 episodes/participant/30 days
Standard Error 0.55
|
|
Total Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 52
|
14.84 episodes/participant/30 days
Standard Error 0.42
|
11.75 episodes/participant/30 days
Standard Error 0.55
|
|
Total Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 78
|
14.33 episodes/participant/30 days
Standard Error 0.42
|
11.43 episodes/participant/30 days
Standard Error 0.55
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic events are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=294 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Percentage of Participants With Total Hypoglycemia Events
Baseline-Week 26
|
99.0 percentage of participants
|
96.9 percentage of participants
|
|
Percentage of Participants With Total Hypoglycemia Events
Baseline-Week 52
|
99.0 percentage of participants
|
96.9 percentage of participants
|
|
Percentage of Participants With Total Hypoglycemia Events
Baseline-Week 78
|
99.0 percentage of participants
|
96.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log \[exposure in days/30\] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=293 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 26
|
1.69 episodes/participant/30 days
Standard Error 0.12
|
2.66 episodes/participant/30 days
Standard Error 0.19
|
|
Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 52
|
1.63 episodes/participant/30 days
Standard Error 0.11
|
2.45 episodes/participant/30 days
Standard Error 0.19
|
|
Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)
Baseline-Week 78
|
1.58 episodes/participant/30 days
Standard Error 0.11
|
2.28 episodes/participant/30 days
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=294 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Percentage of Participants With Nocturnal Hypoglycemic Events
Baseline-Week 26
|
87.4 percentage of participants
|
90.6 percentage of participants
|
|
Percentage of Participants With Nocturnal Hypoglycemic Events
Baseline-Week 52
|
91.5 percentage of participants
|
91.8 percentage of participants
|
|
Percentage of Participants With Nocturnal Hypoglycemic Events
Baseline-Week 78
|
93.5 percentage of participants
|
92.5 percentage of participants
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FSG data at both baseline and post-baseline.
LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=285 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=152 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Fasting Serum Glucose (FSG) by Laboratory Measurement
Week 26
|
138.22 mg/dL
Standard Error 3.80
|
160.35 mg/dL
Standard Error 5.06
|
|
Fasting Serum Glucose (FSG) by Laboratory Measurement
Week 52
|
146.55 mg/dL
Standard Error 4.42
|
164.28 mg/dL
Standard Error 5.72
|
|
Fasting Serum Glucose (FSG) by Laboratory Measurement
Week 78
|
144.64 mg/dL
Standard Error 4.53
|
164.78 mg/dL
Standard Error 5.81
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.
FBG was measured by self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=282 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Fasting Blood Glucose (FBG) Intra-participant Variability
Week 26
|
52.49 mg/dL
Standard Error 1.79
|
59.25 mg/dL
Standard Error 2.43
|
|
Fasting Blood Glucose (FBG) Intra-participant Variability
Week 52
|
53.44 mg/dL
Standard Error 1.85
|
58.15 mg/dL
Standard Error 2.43
|
|
Fasting Blood Glucose (FBG) Intra-participant Variability
Week 78
|
54.87 mg/dL
Standard Error 2.20
|
60.66 mg/dL
Standard Error 2.79
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at baseline and post-baseline.
Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=209 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=112 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion
Week 26
|
-9.92 mg/dL
Standard Error 6.24
|
-14.08 mg/dL
Standard Error 8.75
|
|
0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion
Week 52
|
-6.15 mg/dL
Standard Error 6.91
|
-9.02 mg/dL
Standard Error 9.58
|
|
0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion
Week 78
|
-10.82 mg/dL
Standard Error 8.25
|
-28.94 mg/dL
Standard Error 10.50
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at both baseline and post-baseline.
9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, 52, 65, and 78. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the pre-morning meal the next day. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=271 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=143 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal, Week 26
|
158.58 mg/dL
Standard Error 3.82
|
144.40 mg/dL
Standard Error 5.20
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal, Week 52
|
160.89 mg/dL
Standard Error 4.13
|
152.55 mg/dL
Standard Error 5.38
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal, Week 78
|
163.09 mg/dL
Standard Error 4.66
|
153.38 mg/dL
Standard Error 5.99
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-morning meal, Week 26
|
172.39 mg/dL
Standard Error 4.59
|
165.53 mg/dL
Standard Error 6.44
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-morning meal, Week 52
|
176.32 mg/dL
Standard Error 5.61
|
168.38 mg/dL
Standard Error 7.47
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-morning meal, Week 78
|
183.64 mg/dL
Standard Error 6.23
|
190.54 mg/dL
Standard Error 7.91
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-midday meal, Week 26
|
136.21 mg/dL
Standard Error 3.92
|
153.12 mg/dL
Standard Error 5.33
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-midday meal, Week 52
|
142.82 mg/dL
Standard Error 4.27
|
149.78 mg/dL
Standard Error 5.66
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-midday meal, Week 78
|
150.83 mg/dL
Standard Error 4.90
|
154.56 mg/dL
Standard Error 6.33
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-midday meal, Week 26
|
157.17 mg/dL
Standard Error 4.78
|
164.75 mg/dL
Standard Error 6.69
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-midday meal, Week 52
|
159.59 mg/dL
Standard Error 5.11
|
168.83 mg/dL
Standard Error 6.94
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-midday meal, Week 78
|
154.46 mg/dL
Standard Error 5.76
|
175.52 mg/dL
Standard Error 7.51
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-evening meal, Week 26
|
153.20 mg/dL
Standard Error 4.29
|
168.08 mg/dL
Standard Error 5.75
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-evening meal, Week 52
|
153.01 mg/dL
Standard Error 5.17
|
183.18 mg/dL
Standard Error 6.81
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-evening meal, Week 78
|
149.89 mg/dL
Standard Error 4.92
|
174.50 mg/dL
Standard Error 6.17
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-evening meal, Week 26
|
149.74 mg/dL
Standard Error 5.17
|
191.99 mg/dL
Standard Error 7.20
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-evening meal, Week 52
|
157.81 mg/dL
Standard Error 6.79
|
198.10 mg/dL
Standard Error 9.06
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hours post-evening meal, Week 78
|
163.27 mg/dL
Standard Error 6.07
|
189.43 mg/dL
Standard Error 7.75
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Bedtime, Week 26
|
151.66 mg/dL
Standard Error 4.15
|
176.17 mg/dL
Standard Error 5.63
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Bedtime, Week 52
|
167.35 mg/dL
Standard Error 5.33
|
182.08 mg/dL
Standard Error 7.11
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Bedtime, Week 78
|
165.63 mg/dL
Standard Error 5.37
|
185.45 mg/dL
Standard Error 6.74
|
|
9 Point Self-monitored Blood Glucose (SMBG)
0300 hours, Week 26
|
159.73 mg/dL
Standard Error 5.30
|
163.18 mg/dL
Standard Error 7.50
|
|
9 Point Self-monitored Blood Glucose (SMBG)
0300 hours, Week 52
|
157.52 mg/dL
Standard Error 6.06
|
148.26 mg/dL
Standard Error 8.36
|
|
9 Point Self-monitored Blood Glucose (SMBG)
0300 hours, Week 78
|
165.82 mg/dL
Standard Error 7.19
|
170.35 mg/dL
Standard Error 9.02
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal next day, Week 26
|
149.94 mg/dL
Standard Error 3.74
|
143.89 mg/dL
Standard Error 5.10
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal next day, Week 52
|
155.79 mg/dL
Standard Error 4.24
|
145.55 mg/dL
Standard Error 5.59
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal next day, Week 78
|
156.87 mg/dL
Standard Error 4.80
|
152.63 mg/dL
Standard Error 6.11
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable body weight data at both baseline and post-baseline.
LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=154 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Change From Baseline in Body Weight
Week 26
|
-1.17 kilograms (kg)
Standard Error 0.20
|
0.71 kilograms (kg)
Standard Error 0.27
|
|
Change From Baseline in Body Weight
Week 52
|
-1.22 kilograms (kg)
Standard Error 0.25
|
1.00 kilograms (kg)
Standard Error 0.33
|
|
Change From Baseline in Body Weight
Week 78
|
-0.93 kilograms (kg)
Standard Error 0.28
|
1.04 kilograms (kg)
Standard Error 0.37
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.
Basal insulin dose, short-acting bolus insulin dose (each meal and overall), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C level \[\<100 mg/dL and ≥100 mg/dL\], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=282 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=156 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Basal, Bolus, and Total Insulin Dose
Basal Insulin, Week 26
|
0.40 units/kg/day
Standard Error 0.01
|
0.34 units/kg/day
Standard Error 0.01
|
|
Basal, Bolus, and Total Insulin Dose
Basal Insulin, Week 52
|
0.40 units/kg/day
Standard Error 0.01
|
0.34 units/kg/day
Standard Error 0.01
|
|
Basal, Bolus, and Total Insulin Dose
Basal Insulin, Week 78
|
0.41 units/kg/day
Standard Error 0.01
|
0.35 units/kg/day
Standard Error 0.01
|
|
Basal, Bolus, and Total Insulin Dose
Bolus Insulin, Week 26
|
0.37 units/kg/day
Standard Error 0.01
|
0.46 units/kg/day
Standard Error 0.02
|
|
Basal, Bolus, and Total Insulin Dose
Bolus Insulin, Week 52
|
0.38 units/kg/day
Standard Error 0.01
|
0.47 units/kg/day
Standard Error 0.02
|
|
Basal, Bolus, and Total Insulin Dose
Bolus Insulin, Week 78
|
0.37 units/kg/day
Standard Error 0.02
|
0.48 units/kg/day
Standard Error 0.02
|
|
Basal, Bolus, and Total Insulin Dose
Total Insulin, Week 26
|
0.73 units/kg/day
Standard Error 0.02
|
0.78 units/kg/day
Standard Error 0.02
|
|
Basal, Bolus, and Total Insulin Dose
Total Insulin, Week 52
|
0.74 units/kg/day
Standard Error 0.02
|
0.79 units/kg/day
Standard Error 0.03
|
|
Basal, Bolus, and Total Insulin Dose
Total Insulin, Week 78
|
0.75 units/kg/day
Standard Error 0.02
|
0.80 units/kg/day
Standard Error 0.03
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable lipid data at both baseline and post-baseline.
Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM, adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\] except for the LDL-C outcome variable), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=288 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=152 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Lipid Profile
Cholesterol, Week 26
|
191.86 mg/dL
Standard Error 1.63
|
187.93 mg/dL
Standard Error 2.19
|
|
Lipid Profile
Cholesterol, Week 52
|
190.72 mg/dL
Standard Error 1.59
|
188.65 mg/dL
Standard Error 2.10
|
|
Lipid Profile
Cholesterol, Week 78
|
191.78 mg/dL
Standard Error 1.86
|
190.06 mg/dL
Standard Error 2.39
|
|
Lipid Profile
HDL-C, Week 26
|
61.87 mg/dL
Standard Error 0.59
|
62.75 mg/dL
Standard Error 0.80
|
|
Lipid Profile
HDL-C, Week 52
|
61.01 mg/dL
Standard Error 0.56
|
61.46 mg/dL
Standard Error 0.74
|
|
Lipid Profile
HDL-C, Week 78
|
60.77 mg/dL
Standard Error 0.66
|
61.97 mg/dL
Standard Error 0.85
|
|
Lipid Profile
LDL-C, Week 26
|
108.85 mg/dL
Standard Error 1.33
|
108.31 mg/dL
Standard Error 1.79
|
|
Lipid Profile
LDL-C, Week 52
|
109.40 mg/dL
Standard Error 1.39
|
109.74 mg/dL
Standard Error 1.84
|
|
Lipid Profile
LDL-C, Week 78
|
109.62 mg/dL
Standard Error 1.62
|
110.35 mg/dL
Standard Error 2.09
|
|
Lipid Profile
Triglycerides, Week 26
|
109.64 mg/dL
Standard Error 3.89
|
85.35 mg/dL
Standard Error 5.24
|
|
Lipid Profile
Triglycerides, Week 52
|
105.17 mg/dL
Standard Error 3.64
|
87.94 mg/dL
Standard Error 4.80
|
|
Lipid Profile
Triglycerides, Week 78
|
110.80 mg/dL
Standard Error 4.78
|
88.96 mg/dL
Standard Error 6.14
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable anti-LY2605541 antibody data at baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
The percentage of participants with a treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable or from detectable to the value with at least 130% relative increase from baseline.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=288 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=153 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Week 26
|
30.6 percentage of participants
|
15.8 percentage of participants
|
|
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Week 52
|
29.9 percentage of participants
|
17.1 percentage of participants
|
|
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Week 78
|
26.4 percentage of participants
|
13.1 percentage of participants
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable ITSQ data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification (baseline HbA1c \[≤8.5% or \>8.5%\] and country) as fixed effects and baseline value of the dependent variable as a covariate.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=273 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=149 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ)
|
72.43 units on a scale
Standard Error 0.69
|
73.91 units on a scale
Standard Error 0.94
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline.
LBSS (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) is a 33-item questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\] and country), visit, treatment-by-visit interaction , and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=287 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=151 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Low Blood Sugar Survey (LBSS)
Week 26
|
28.09 units on a scale
Standard Error 0.70
|
27.09 units on a scale
Standard Error 0.95
|
|
Low Blood Sugar Survey (LBSS)
Week 52
|
27.76 units on a scale
Standard Error 0.77
|
27.00 units on a scale
Standard Error 1.01
|
|
Low Blood Sugar Survey (LBSS)
Week 78
|
27.68 units on a scale
Standard Error 0.91
|
27.14 units on a scale
Standard Error 1.18
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using a 3-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using ANCOVA, adjusting for treatment and stratification factors (baseline HbA1c \[≤8.5% or \>8.5%\] and country) as fixed effects and baseline EQ-5D score as a covariate.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=277 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=150 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
European Quality of Life-5 Dimension (EQ-5D)
|
0.92 units on a scale
Standard Error 0.01
|
0.91 units on a scale
Standard Error 0.01
|
SECONDARY outcome
Timeframe: 26 weeks and 78 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable RAPA data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.
The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activities, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility (flex) activity, either strength or flex (not both), both strength and flex activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, then multiplying by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=98 Participants
LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=57 Participants
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Sedentary, Week 26
|
1.0 percentage of participants
|
0.0 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Sedentary, Week 78
|
1.3 percentage of participants
|
0.0 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Underactive, Week 26
|
3.1 percentage of participants
|
3.5 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Underactive, Week 78
|
3.8 percentage of participants
|
2.0 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Light activity, Week 26
|
13.3 percentage of participants
|
10.5 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Light activity, Week 78
|
7.5 percentage of participants
|
13.7 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Regular underactive, Week 26
|
24.5 percentage of participants
|
29.8 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Regular underactive, Week 78
|
31.3 percentage of participants
|
29.4 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Active, Week 26
|
58.2 percentage of participants
|
56.1 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Active, Week 78
|
56.3 percentage of participants
|
54.9 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Neither strength/flex, Week 26
|
35.7 percentage of participants
|
43.9 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Neither strength/flex, Week 78
|
37.0 percentage of participants
|
47.1 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Either strength/flex, Week 26
|
30.6 percentage of participants
|
35.1 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Either strength/flex, Week 78
|
33.3 percentage of participants
|
29.4 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Both strength/flex, Week 26
|
33.7 percentage of participants
|
21.1 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Both strength/flex, Week 78
|
29.6 percentage of participants
|
23.5 percentage of participants
|
Adverse Events
LY2605541 + Insulin Lispro
Glargine + Insulin Lispro
Serious adverse events
| Measure |
LY2605541 + Insulin Lispro
n=294 participants at risk
LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered subcutaneously via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 participants at risk
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Muscle contracture
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Osteomyelitis
|
0.68%
2/294 • Number of events 4
|
0.63%
1/159 • Number of events 3
|
|
Cardiac disorders
Atrial fibrillation
|
1.0%
3/294 • Number of events 4
|
0.63%
1/159 • Number of events 1
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/294
|
0.63%
1/159 • Number of events 4
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Faeces pale
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/294
|
0.63%
1/159 • Number of events 2
|
|
Gastrointestinal disorders
Pancreatitis
|
0.68%
2/294 • Number of events 2
|
0.00%
0/159
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Gastrointestinal disorders
Small intestinal perforation
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Immune system disorders
Anaphylactic shock
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Abscess limb
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Cellulitis
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Infections and infestations
Chronic sinusitis
|
0.34%
1/294 • Number of events 3
|
0.00%
0/159
|
|
Infections and infestations
Diabetic gangrene
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.68%
2/294 • Number of events 2
|
0.00%
0/159
|
|
Infections and infestations
Infectious mononucleosis
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Infections and infestations
Pneumonia
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Pneumonia bacterial
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Post procedural sepsis
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Pseudomonas infection
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Infections and infestations
Sepsis
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Injury, poisoning and procedural complications
Alcohol poisoning
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Injury, poisoning and procedural complications
Incorrect dose administered
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Overdose
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.34%
1/294 • Number of events 1
|
0.63%
1/159 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
15.3%
45/294 • Number of events 73
|
8.2%
13/159 • Number of events 20
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Metabolism and nutrition disorders
Metabolic disorder
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.34%
1/294 • Number of events 1
|
0.63%
1/159 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Musculoskeletal and connective tissue disorders
Spondylolisthesis
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign bone neoplasm
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.64%
1/157 • Number of events 1
|
0.00%
0/73
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
1.3%
2/157 • Number of events 5
|
0.00%
0/73
|
|
Nervous system disorders
Complicated migraine
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.34%
1/294 • Number of events 3
|
0.00%
0/159
|
|
Psychiatric disorders
Adjustment disorder
|
0.34%
1/294 • Number of events 3
|
0.00%
0/159
|
|
Psychiatric disorders
Suicide attempt
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Renal and urinary disorders
Urinary incontinence
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Reproductive system and breast disorders
Cervical polyp
|
0.64%
1/157 • Number of events 2
|
0.00%
0/73
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.64%
1/157 • Number of events 2
|
0.00%
0/73
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.64%
1/157 • Number of events 2
|
0.00%
0/73
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.34%
1/294 • Number of events 1
|
0.00%
0/159
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.68%
2/294 • Number of events 5
|
0.00%
0/159
|
|
Surgical and medical procedures
Hysterectomy
|
0.64%
1/157 • Number of events 1
|
0.00%
0/73
|
|
Surgical and medical procedures
Toe amputation
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Vascular disorders
Intermittent claudication
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.34%
1/294 • Number of events 2
|
0.00%
0/159
|
|
Vascular disorders
Peripheral artery stenosis
|
0.00%
0/294
|
0.63%
1/159 • Number of events 1
|
Other adverse events
| Measure |
LY2605541 + Insulin Lispro
n=294 participants at risk
LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered subcutaneously via pen device at meal times for 78 weeks.
|
Glargine + Insulin Lispro
n=159 participants at risk
Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
|
|---|---|---|
|
Infections and infestations
Gastroenteritis viral
|
1.4%
4/294 • Number of events 4
|
3.1%
5/159 • Number of events 6
|
|
Infections and infestations
Influenza
|
8.5%
25/294 • Number of events 32
|
8.8%
14/159 • Number of events 14
|
|
Gastrointestinal disorders
Diarrhoea
|
4.4%
13/294 • Number of events 15
|
1.9%
3/159 • Number of events 3
|
|
Infections and infestations
Bronchitis
|
3.7%
11/294 • Number of events 12
|
2.5%
4/159 • Number of events 4
|
|
Infections and infestations
Cystitis
|
3.1%
9/294 • Number of events 10
|
1.9%
3/159 • Number of events 3
|
|
Infections and infestations
Gastroenteritis
|
3.7%
11/294 • Number of events 11
|
5.0%
8/159 • Number of events 9
|
|
Infections and infestations
Nasopharyngitis
|
31.3%
92/294 • Number of events 152
|
23.9%
38/159 • Number of events 61
|
|
Infections and infestations
Pharyngitis
|
4.4%
13/294 • Number of events 19
|
4.4%
7/159 • Number of events 9
|
|
Infections and infestations
Upper respiratory tract infection
|
4.4%
13/294 • Number of events 22
|
7.5%
12/159 • Number of events 17
|
|
Infections and infestations
Urinary tract infection
|
5.1%
15/294 • Number of events 17
|
5.0%
8/159 • Number of events 14
|
|
Investigations
Alanine aminotransferase increased
|
4.1%
12/294 • Number of events 20
|
0.63%
1/159 • Number of events 1
|
|
Investigations
Weight increased
|
1.4%
4/294 • Number of events 4
|
3.8%
6/159 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.1%
15/294 • Number of events 17
|
4.4%
7/159 • Number of events 7
|
|
Nervous system disorders
Headache
|
6.1%
18/294 • Number of events 27
|
6.3%
10/159 • Number of events 13
|
|
Psychiatric disorders
Depression
|
0.68%
2/294 • Number of events 2
|
3.1%
5/159 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.1%
9/294 • Number of events 12
|
3.1%
5/159 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Lipodystrophy acquired
|
5.8%
17/294 • Number of events 24
|
0.63%
1/159 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Lipohypertrophy
|
15.3%
45/294 • Number of events 66
|
0.00%
0/159
|
|
Vascular disorders
Hypertension
|
3.4%
10/294 • Number of events 10
|
0.63%
1/159 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60